“Women with ovarian cancer are dying because GPs are failing to detect the early signs of the disease,” reported The Times. A study has suggested that family doctors may be overlooking one of the main symptoms...

“Women with ovarian cancer are dying because GPs are failing to detect the early signs of the disease,” reported The Times. A study has suggested that family doctors may be overlooking one of the main symptoms, a distended abdomen, because it is not included in the guidance on which symptoms need urgent investigation, said the story in The Times.

This well-designed study identified symptoms that women with ovarian cancer commonly report to their GPs in the year before diagnosis. It identified seven key symptoms, particularly abdominal distension, abdominal pain and urinary frequency.

Despite what was reported in the newspapers, this study into the risks of ovarian cancer does not indicate that symptoms are being missed by GPs, as the patient data it used was limited and did not include the patient’s history or the outcome of consultation. However, the study draws attention to the need for all doctors to suspect ovarian cancer in women with abdominal distension (bloating), and to evaluate carefully urinary or gynaecological symptoms or general symptoms, such as loss of appetite, that may otherwise be assumed to be from another cause.

Where did the story come from?

This research was carried out by Dr William Hamilton and colleagues from the National Institute for Health Research (NIHR) School for Primary Care Research at the University of Bristol. The study was funded by the Department of Health’s NIHR School for Primary Care Research funding scheme and published in the peer-reviewed British Medical Journal.

What kind of scientific study was this?

The aim of this case control study was to identify and quantify the symptoms that women with ovarian cancer report to their GP in the year before they are diagnosed.

Using the records of 39 general practices in Devon and Exeter, the researchers searched for all women aged 40 or over who were diagnosed with ovarian cancer between 2000 and 2007. They found 97,500 women in this age group, of whom 255 had been diagnosed with ovarian cancer or suspected ovarian cancer. After excluding 43 women for a number of reasons, such as other malignancies, benign disease, diagnosis before 2000 and those who had moved out of the area, 212 cases were available for analysis.

Diagnosis of ovarian cancer was taken as positive test results (available for 80%) or diagnosis by a specialist. At the time of the study, 113 of the diagnosed women (53%) had already died. Each case was matched to five age-matched controls without ovarian cancer (1,060 following exclusions; average age 67).

The medical records for each case and control were collected and made anonymous. Three researchers, who were unaware which patients had been diagnosed with cancer (blinded), coded all symptoms recorded in consultations in the year prior to the date of diagnosis.

Only symptoms present in more than 5% of cases and controls were included in the analyses. A positive predictive value (PPV) was calculated for each symptom (or combination of symptoms). Positive predictive value is the probability that someone who has the symptom (or combination of symptoms) actually has ovarian cancer.

What were the results of the study?

Seven symptoms were more common in women diagnosed with ovarian cancer:

Abdominal distension: PPV 2.5% (95% CI: 1.2% to 5.9%)

Postmenopausal bleeding: PPV 0.5% (0.2% to 0.9%)

Loss of appetite: PPV 0.6% (0.3% to 1.0%)

Increased urinary frequency: PPV 0.2% (0.1% to 0.3%)

Abdominal pain: PPV 0.3% (0.2% to 0.3%)

Rectal bleeding: PPV 0.2% (0.1% to 0.4%)

Abdominal bloating: PPV 0.3% (0.2% to 0.6%)

In the year before diagnosis, 85% of cases and 15% of controls reported to their GP with at least one of the symptoms. When the analysis was confined to symptoms reported more than six months before date of diagnosis, abdominal distension, abdominal pain and having to urinate often were still associated with ovarian cancer (meaning that the other symptoms were more commonly reported nearer to the time of diagnosis).

On examination of the patient, signs associated with a diagnosis of ovarian cancer were a lump in the abdomen, or a lump that could be felt during vaginal or rectal examination, and abdominal tenderness. Women diagnosed with ovarian cancer had visited their GP on more occasions in the past year than the controls (average 10 occasions compared with six).

What interpretations did the researchers draw from these results?

The researchers conclude that women with ovarian cancer usually have symptoms and have reported them to primary care, sometimes several months prior to diagnosis. They say that this study provides “an evidence base for selection of patients for investigation, both for clinicians and for developers of guidelines”.

What does the NHS Knowledge Service make of this study?

This well-designed study investigated the symptoms that women with ovarian cancer went to their GP with in the year before diagnosis. It identified seven key symptoms reported more frequently in women who were later diagnosed with ovarian cancer. Principally, these were abdominal distension, abdominal pain and having to urinate often. When considering this, a couple of points should be kept in mind:

All symptoms except for abdominal distension had positive predictive values below 1%. These are low values and mean that the chance of any individual with these symptoms having cancer is low (less than one in 100). This is because there is a high frequency of abdominal symptoms in the healthy population and also a relatively low incidence of ovarian cancer. The researchers say that about 35 new cases of ovarian cancer a year could be expected in this population of 39 practices, which is about one a year for each practice.

Other features may be suggestive of ovarian cancer, such as increased age and reproductive and menstrual history. When these are noted in the presence of a symptom such as abdominal distension, the combination, along with certain features of medical history and examination findings, may give a higher positive predictive value than that given for one symptom alone. For example, while abdominal distension has a fairly low PPV for ovarian cancer, the combination of abdominal distension, postmenopausal bleeding, abdominal mass and being aged over 60 is likely to have a far higher PPV.

The false positive rate cannot be calculated for this study. This is the number of women who were sent for further testing but who did not have ovarian cancer.

Despite the newspaper headlines, this study cannot clarify whether symptoms of ovarian cancer are being inappropriately missed and leading to a delay in diagnosis. This is because it only used the records of individual symptoms (or symptom pairs) reported to GPs in the year before diagnosis. Other details, including the severity or duration of the symptoms, past medical history, examination findings and outcome of the consultation were not analysed. If they had been, then it would have been possible to say whether the doctor had valid reasons for considering other diagnoses. Likewise, it is not possible to tell whether the GP was considering ovarian cancer and referred a patient for further specialist assessment as a result of the presentation of this symptom.

The symptoms had been recorded in medical notes and there may be some overlap in terminology between clinicians and GP surgeries. For example, abdominal distension and abdominal bloating are unlikely to be two distinct symptoms.

By identifying cases through database coding, it is possible that some diagnoses were missed.

Only 39 practices in one region of the country were considered and it cannot be assumed that the findings reflect the situation elsewhere in the UK, where there may have been different findings.

These are not the only symptoms of ovarian cancer. Women can have a variety of symptoms and present to GPs with just one symptom in isolation or several in combination. The researchers have only considered those reported most often and mainly considered them as isolated symptoms. In practice, all symptoms and signs on examination would be considered in relation to the medical history.

This important study draws attention to the need for healthcare practitioners to consider ovarian cancer in women presenting with the symptoms highlighted by this study. Further analysis is needed to investigate symptom combinations, the influence of age and the thresholds for referral.